Enthesitis

Definition

Enthesis describes the point of origin or attachment of a tendon, ligament, fascia or, for example, a joint capsule to bone. Entheses exist everywhere in the body, not only in the periphery, but also axially, respectively at the spine. "Fibrous" entheses are characterized by the direct insertion of a tendon or muscle on the bone and are located in thick cortical layers, which we typically find in diaphyses of long bones. "Fibrocartilaginous" entheses insert at thin cortical layers that occur at the epiphyseal or apophyseal ends of long bones and are often located near joints with synovial tissue (e.g., bursa, synovial recessus). Typically, a tendon or ligament, for example, passes over a bony "pulley" covered by hyaline cartilage at these sites just before the entheseal insertion. In the layer of the enthesis facing the "pulley", there is histologically a "sesamoid" cartilage and in between there is often a synovial structure (e.g., bursa or synovial membranes of a joint).

Enthesitis itself is an acute or chronic inflammation of tendons at their insertion point and is characteristically found in patients with spondylarthritis (SpA), psoriatic arthritis (PsA) and in the context of other spondyloarthritides. Histological studies suggest that the enthesis can be considered as an organ. The term "enthesis organ" or "synovio-enthesis complex" includes not only the enthesis insertion itself, but also adjacent structures, such as bursae or adjacent adipose tissue.

Definition of "enthesis organ":

• Origin or attachment of tendon/ligament/fascia/capsule.

• Sesamoid fibrocartilage

• Entheseal fibrocartilage

• Periosteal fibrocartilage

• Adjoining fat pad

• Bursa

• Synovial recessus

Aetiology

We usually see enthesitis in the context of an underlying disease with inflammation at the level of the enthese. Enthesitis may also be the consequence of repeated mechanical overloading, which typically occurs in active, otherwise healthy patients [1].

As a rule, we associate enthesitis with spondyloarthritis. This includes the following diseases, among others:

• Axial spondyloarthritis (axSpA): early non-radiographic/radiographic spondyloarthritis, ankylosing spondylitis.

• Peripheral spondyloarthritis (pSpA)

• Reactive arthritis (ReA)

• Psoriatic arthritis (PsA)

• Undifferentiated spondyloarthritis (uSpA)

• Enterohepatic spondyloarthritis (eSpA)

• Spondyloarthritis with primary enthesitis, e.g., juvenile spondyloarthritis

• SAPHO syndrome (synovitis-acne-pustulosis-hyperostosis-osteitis syndrome)

However, it is extremely important to note that enthesitis is not unique to the above-mentioned spondyloarthritides. This in turn implies that the finding is nonspecific.

Inflammatory entheseal involvement can occur in different diseases (examples: endocrinopathies, mechanical stress, vasculitis, osteoarthritis, drug associated, isolated juvenile arthritis, IgG4 associated, DISH, familial Mediterranean fever).

In addition, on imaging, changes also occur in asymptomatic healthy individuals and depend on age, physical activity, body mass index, and are more common in men than in women [2].

How much a role mechanical stress plays in the pathological mechanisms of pSpA and PsA remains unclear. However, no counter evidence has been proposed as to why processes in these systemic diseases are fundamentally different from isolated enthesitis as the lower limb is affected more often [1]. One hypothesis is a lowered threshold in developing enthesitis in patients with SpA and PsA [1]. This could be explained by a prolonged immune activation due to the IL-23-IL-17 pathway, which acts as an amplifier of a range of cytokines and other pro-inflammatory mediators [1].

Due to a variety of mediators, entheseal inflammation is accompanied by astonishing tissue proliferation in form of local apposition of periosteal bone at enthseal sites (enthesophytes) [1].

Epidemiology

There is very limited data on shoulder involvement in patients with SpA. A study about axial SpA has found that the rotator cuff is involved in 7% to 33% of patients with the prevalence increasing the longer the patients suffer from axial SpA [3]. Generally, excessive weight, active joint disease and young age are linked to the occurrence of enthesitis [1].

In clinical practice, we often see enthesitis in the context of spondyloarthritis at the origin of the deltoid muscle at the acromion and in the area of insertion of the supraspinatus tendon.

History

Anamnesis is used to gain insight on the patient’s family history and looking for other signs that might indicate a specific underlying cause.

Disease specific diagnosis

The examiner should inspect, palpate and asses the range of motion of the glenohumeral as well as the acromioclavicular joint [3]. Clinical diagnosis is complicated by the ambiguity of presentation [1-4]. Differentiating between enthesitis and synovitis can therefore pose a real challenge. Fortunately, advances in imaging technologies have led to a more sensitive and specific way of diagnosing enthesitis [4].

Radiographic findings in x-rays can be used to divide shoulder involvement in SpA patients into two different forms:

The non-destructive and the destructive form. In non-destructive SpA of the shoulder, humeral head ankylosis and ossification of the coracoclavicular ligament can be described. For the destructive form, the characteristic is erosion of the humeral head (hatchet-sign) due to enthesitis. The acromioclavicular joint involvement can be seen as degenerative changes in the x-ray [3].

The clinical diagnosis of enthesitis is poor in terms of sensitivity and specificity, so imaging techniques, including magnetic resonance imaging (MRI) or high-resolution sonography, are used.

MRI findings range from bone marrow edema (BME) of the acromion and the greater tuberosity to entheseal BME in point of origin, respectively insertion of the deltoid and supraspinatus tendon [3].

Ultrasound is used to evaluate enthesitis in form of tendon thickening, bony erosion and enthesophytes [3]. Additionally, Doppler signal allows the examiner to gain insight of inflammatory processes [1]. Glenohumeral synovitis on the other hand is not often seen in SpA [3].

If we take MRI as the gold standard, the sensitivity is 0.93 versus 0.58 and the specificity is 0.92 versus 0.84 when comparing ultrasound versus clinical examination. In recent years, many and sometimes different sonographic definition attempts have been published. Ultrasound enthesitis definitions mentioned the following ultrasound findings:

• Increase in thickness of the tendon (94%).

• Hypoechogenicity of the tendon (83 %)

• Enthesophyte (69 %)

• Erosion (67 %)

• Calcification (52 %)

• Bursitis (46 %)

• Cortical irregularity (29 %)

• Doppler signal (46 %)

All of the above sonomorphologic findings are not 100% specific for SpA-associated enthesitis and may be present in all of the aforementioned conditions. Another problem with these different findings is that they represent different entities of enthesitis. Some indicate ongoing inflammatory activity (which is potentially reversible) and others are more indicative of chronic and presumably irreversible damage, respectively, indicating repair processes [2].

Signs of inflammation on ultrasound:

• Hypoechogenicity and loss of homogeneous fibrillar pattern of the enthesis-near tendon and fibrocartilage (subjective qualitative description and therefore dependent on the probe angle and gain setting of the machine).

• Increase in thickness

• Doppler activity (e.g., in B-flow mode, color Doppler or power Doppler)

Signs of damage in ultrasound:

• Calcifications, hyperechoic

• Enthesophytes (usually at the most poorly vascularized distal site).

• Erosions, often found under the more proximal area of tendon insertions and related to biomechanical factors.

Differential Diagnosis

• Synovitis of the glenohumeral joint

• Osteoarthritis

• Myofascial pain

The prognosis and further course of the underlying disease depends in each case on the underlying primary disease